Source of a micro-nutrient in a semi-synthetic basal diet as a causative factor in inducing urinary calculi in rats and its inhibition by PSC 833, a potent inhibitor of P-glycoprotein

We report a serendipitous finding of urinary calculi in rats fed a semi-synthetic basal diet. This observation was made during ongoing studies to evaluate the inhibitory effect of PSC 833, a potent inhibitor of P-glycoprotein, on development of tumors in rodent tumor model systems. A large number of...

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Bibliographic Details
Published in:Comparative medicine 2003-08, Vol.53 (4), p.444-447
Main Authors: Kankesan, Janarthanan, Vanama, Ramesh, Renlund, Richard, Thiessen, Jake J, Ling, Victor, Rao, Prema M, Rajalakshmi, Srinivasan, Sarma, Dittakavi S.R
Format: Article
Language:English
Subjects:
Animals
ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors
bladder
choline
Choline - administration & dosage
Choline - adverse effects
Cyclosporins - administration & dosage
diet
Female
Food, Formulated - adverse effects
Male
necropsy
neoplasms
pelvis
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
risk
Rodent Diseases - etiology
Rodent Diseases - prevention & control
specific pathogen-free animals
Specific Pathogen-Free Organisms
urinary calculi
Urinary Calculi - etiology
Urinary Calculi - prevention & control
Urinary Calculi - veterinary
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Summary:We report a serendipitous finding of urinary calculi in rats fed a semi-synthetic basal diet. This observation was made during ongoing studies to evaluate the inhibitory effect of PSC 833, a potent inhibitor of P-glycoprotein, on development of tumors in rodent tumor model systems. A large number of specific-pathogen-free (SPF) female Sprague-Dawley and SPF male Fischer 344 rats being fed the diet were euthanized when it became evident clinically that they were uremic. At necropsy, the renal pelvis, ureters, and urinary bladder contained numerous calculi. The presence of urinary calculi was determined to be related to the source of a Food Chemical Codex grade of choline bitartrate. Rats being fed the same basal diet containing the United States Pharmacopia grade of choline bitartrate failed to develop urinary calculi. Interestingly, rats treated with the P-glycoprotein inhibitor were at significantly reduced risk of developing urinary calculi. This finding highlights how something seemingly innocuous as a minor dietary constituent can have a profound impact and, thereby, affect experimental outcome.
ISSN:1532-0820
2769-819X